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Study to Evaluate the Safety and Effect of HIVconsv Vaccines in Combination With Histone Deacetylase Inhibitor Romidepsin on the Viral Rebound Kinetic After Treatment Interruption in Early Treated HIV-1 Infected Individuals

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ClinicalTrials.gov Identifier: NCT02616874
Recruitment Status : Completed
First Posted : November 30, 2015
Last Update Posted : January 17, 2018
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Hospital Clinic of Barcelona
Hospital de Sant Pau
HIVACAT
University of Oxford
BCN Checkpoint
Information provided by (Responsible Party):
IrsiCaixa

Study Description
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Brief Summary:
The BCN02-Romi study aims to evaluate a combined "kick and kill" strategy using the most immunogenic candidate vaccine available so far (HIVconsv) with the strongest latency reversal agent available at present time (romidepsin) in a cohort of early-treated HIV positive individuals.

Condition or disease Intervention/treatment Phase
HIV Drug: MVA.HIVconsv vaccine Drug: Romidepsin Phase 1

Detailed Description:
The combined use of therapeutic vaccination and specific drugs that can reactivate latent virus from the reservoir (Kick and kill strategies) hold the promise to achieve functional cure and viral eradication of HIV infection. The present project consists of a proof-of-concept clinical trial in a cohort of 24 early treated HIV-1 infected individuals rolled-over from the BCN01 vaccine clinical trial in which participants received the most immunogenic vaccines tested to date, ChAd and modified vaccinia Ankara (MVA).HIVconsv vaccines. All individuals will be given a booster immunization with MVA.HIVconsv in combination with romidepsin (RMD), a potent histone deacetylation inhibitor (HDACi) and will later undergo a monitored antiretroviral pause. HIVconsv vaccines have specifically been designed to stimulate a broad and potent cytotoxic T cell (CTL) response towards the most conserved viral regions of the HIV-1 proteome, which have recently been suggested to have a crucial role when targeting HIV variants harboured in the latent reservoir with mutations to escape T-cell immune responses. The study includes the development of a population pharmacokinetic/pharmacodynamic (PK/PD) substudy to analyse the in vivo effects of RMD in the induction of HIV expression in resting cells, deeply investigate any unintended effect on the CTL function as well as predict the relationship between RMD exposure and such effects. The investigators' results will allow investigators to optimize RMD dosing, to evaluate the clinical efficacy of this eradication strategy after the cART interruption and to identify better correlates of control of rebound viremia after cessation of treatment.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase I Trial to Evaluate the Safety and Effect of HIVconsv Vaccines in Combination With Histone Deacetylase Inhibitor Romidepsin on the Viral Rebound Kinetic After Treatment Interruption in Early Treated HIV-1 Infected Individuals (BCN02-Romi)
Study Start Date : February 2016
Actual Primary Completion Date : September 2016
Actual Study Completion Date : October 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Romidepsin

Arms and Interventions
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Arm Intervention/treatment
Experimental: MVA.HIVconsv plus romidepsin
MVA.HIVconsv plus romidepsin
 Drug: MVA.HIVconsv vaccine
Dose: 2x10e8 pfu, Interval: weeks 0 and 9.

Drug: Romidepsin
Dose: 5mg/m2 over 4hours, Interval: weeks 3, 4 and 5


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with grade >=3 adverse events assessed by Division of AIDS (DAIDS) grading table [ Time Frame: Through study completion, maximum 75 weeks ]
    Grade >=3 adverse events

  2. Number of participants with serious adverse events [ Time Frame: Through study completion, maximum 75 weeks ]
    Serious adverse events

  3. Viral reservoir measured by total HIV-1 DNA copies per 10e6 CD4+ T cells [ Time Frame: From baseline to visit week 6 (romidepsin 3 + 1 week) ]
    Total HIV-1 DNA copies per 10e6 CD4+ T cells


Secondary Outcome Measures :
  1. Romidepsin Cmax [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS)

  2. Romidepsin Cmax [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  3. Romidepsin Cmax [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  4. Romidepsin Cmin [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  5. Romidepsin Cmin [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  6. Romidepsin Cmin [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  7. Romidepsin area under curve (AUC) [ Time Frame: week 3 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  8. Romidepsin AUC [ Time Frame: week 4 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  9. Romidepsin AUC [ Time Frame: week 5 ]
    RMD plasma concentrations will be measured by LC-MS/MS

  10. HIV-1 expression in resting CD4+ T-cells measured by CA-RNA and single-copy assay (SCA) [ Time Frame: week 6 ]
  11. Levels of Histone H3 acetylation in lymphocytes [ Time Frame: week 6 ]
  12. CTL toxicity assessment based on viability, activation or exhaustion (most relevant marker according to previous studies) [ Time Frame: week 6 ]
  13. HIVconsv-specific T cell responses will be measured by IFNg ELISPOT using peptide pools covering different HIV proteins and HIVcons sequences. [ Time Frame: week 6 ]
  14. Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay [ Time Frame: Baseline ]
  15. Viral suppressive capacity of CD8+ T cells in vitro, using a flow cytometric assay [ Time Frame: Week 17 ]
  16. Proportion of individuals who initiate a MAP following the futility analysis [ Time Frame: Week 17 ]
  17. Proportion of individuals who maintain sustained plasma viral load (pVL) <2,000 copies/ml [ Time Frame: Week 29 ]
  18. Proportion of individuals in whom cART is reinitiated due to viral rebound [ Time Frame: Up to 51 weeks ]
  19. Emergence of viral resistance during MAP phase [ Time Frame: Up to 51 weeks ]
    Description of viral resistance emerged, genotype.

  20. Proportion of patients with viral suppression 6 months after treatment resumption. [ Time Frame: 24 weeks after treatment resumption (up to 75 weeks). ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject included in ChAd-MVA.HIVconsv_BCN01 study with complete follow-up and included in BCN01-RO extension study.
  2. Optimal virological suppression for at least 3 years.cop/ml).
  3. Being on a non-boosted integrase-inhibitor based regimen (raltegravir or dolutegravir) for at least 4 weeks at screening visit.

  4. Haematological and biochemical laboratory parameters as follows:

    • Haemoglobin > 10g/dl
    • Platelets > 100.000/dl
    • Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
    • Creatinine ≤ 1.3 x ULN
  5. CD4 T cell count ≥500 cells/mm3

Exclusion Criteria:

  1. Positive pregnancy test.
  2. Presence of resistance drug mutations in the screening genotype
  3. History of autoimmune disease other than HIV-related auto-immune disease.
  4. Treatment for cancer or lymphoproliferative disease within 1 year of study entry
  5. Any other prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
  6. Current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02616874


Locations
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Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Clinic Hospital
Barcelona, Spain, 08036
Sponsors and Collaborators
IrsiCaixa
Germans Trias i Pujol Hospital
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Hospital Clinic of Barcelona
Hospital de Sant Pau
HIVACAT
University of Oxford
BCN Checkpoint
More Information
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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Responsible Party: IrsiCaixa
ClinicalTrials.gov Identifier: NCT02616874    
Other Study ID Numbers: BCN02-Romi
First Posted: November 30, 2015    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Keywords provided by IrsiCaixa:
HIV infection
Early treatment
Romidepsin
HDACi
 Therapeutic Vaccines
HIVconsv
HIV reservoir
Population PK/PD analysis
Additional relevant MeSH terms:
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Romidepsin
Antibiotics, Antineoplastic
Antineoplastic Agents